The present invention relates to a powder pharmaceutical formulation, which may be used as a carrier vehicle for the administration of drugs. The powder pharmaceutical formulation of the present invention is particularly adapted for administration as an insufflation into a body cavity. Specifically, such formulation can be used in dry powder inhalers for pulmonary delivery. Examples of drugs for pulmonary delivery are albuterol sulfate, ipratropium bromide and tiotropium bromide. However, other drugs may be incorporated into the formulation of the present invention.
Capsules are frequently used as a storage means for finely divided, pharmaceutical powders comprising active drug that is to be delivered to a patient via inhalation. For example, to avoid the use of propellant gases, some of which (chloro-fluoro-carbons or CFCs) have been implicated in environmental damage (depletion of the ozone layer in the atmosphere), dry powder comprising an active drug constituent is placed into a capsule. The capsule is loaded into a dry powder inhaler (DPI), the inhaler is used to administer the drug product. Generally, such devices cut or pierce the capsules comprising the dry powder prior to administration, and the powder is then inhaled by the patient.
The capsules usually consist of two (2) halves that are usually supplied by the capsule manufacturer in an assembled (closed) but not locked state. During capsule filling, the two halves are separated, filled with the pharmaceutical powder formulation comprising the active drug, and then closed and locked for insertion into the DPI. Often, the capsule is a hard, gelatin capsule. Hard cellulose and plastic capsules suitable for storing pharmaceutical powders are also used. Such capsules are available from Capsugel (Belgium), Su-Heung (South Korea) and Elamco (United States), among other manufacturers.
Where the active drug in the powdered pharmaceutical formulation is to be delivered to the upper, respiratory tract (i.e., intranasally), the particles of active drug should be about 20 to about 100 micrometers in size. Where administration of the active drug is to be to the lower respiratory tract (i.e., intrapulmonary), the particles of active drug are preferably less than about 5 micrometers in size.
Such small sizes present handling problems (i.e., filling the capsules during manufacture), so the active drug is usually mixed with a coarse carrier. The carrier is typically a soluble hexose such as glucose or lactose, or mannitol. The carrier also functions as a bulking agent for an active drug having a low dose regimen. See, for example, U.S. Pat. No. 5,254,335. Additionally, many drugs used in inhalation therapy are given in small doses regardless, i.e., less than about 250 micrograms, and so bulking agents are routinely used.
Ipratropium bromide is an active drug that is typically administered via inhalation. It presents problems for use in DPIs since the amount of ipratropium bromide to be administered is very low ( less than 50 micrograms). Accordingly, ipratropium bromide must be blended with a bulking agent, such as lactose or glucose, for administration via DPIs.
The soluble hexoses used as carriers for inhalable drugs are non-toxic and tend to be stable in the presence of active drug substance. However, the soluble hexoses tend to be hygroscopic and require special packaging to prevent moisture from contacting the powdered formulation, and thereby causing the formulation to become unusable due to caking and lump formation.
The applicant has discovered that certain non-toxic and pharmaceutically acceptable powdered materials have reduced sensitivity to moisture, but also have the requisite biocompatibility that permits the use of these non-toxic, pharmaceutically acceptable powdered materials as a vehicle for the formulation of an insufflation.
The invention provides an insufflation for the administration of a drug into a body cavity. The dosage form comprises an effective amount of a drug, which is active when administered as an insufflation, and a carrier powder which is a finely divided powder selected from the group consisting of myo-inositol, mannitol and cellobiose. The invention also includes a method of administering a drug as an insufflation which comprises administering into a body cavity an effective amount of a drug dispersed in a finely divided powder selected from the group consisting of myo-inositol, mannitol, cellobiose and mixtures thereof.
Accordingly, it is a primary object of the invention to provide a novel drug powder formulation, which may be administered as an insufflation.
It is also an object of the invention to provide a stable, free-flowing composition of a drug, which will resist the effect of moisture and high humidity, can be dispensed as an insufflation.
It is also an object of the invention to provide a method for the administration of a drug in a powder formulation, which permits administration of the drug as an insufflation.
These other objects of the invention will become apparent from the specification hereinafter presented.